Opioid dependence (OD) is a common disorder resulting in considerable social, medical and psychiatric disability, both in the U.S. and internationally. Current data demonstrate the importance of genetic factors in its etiology, and there is a strong expectation of genetic heterogeneity and complex inheritance. To date, no human research has unequivocally established locations of genes contributing to OD. However, advances in methods for the genetic analysis of complex traits, and recent successes in identifying genes for common diseases in specialized (e.g., isolated) populations, make this an optimal time to initiate such a study. Our group has traveled to the "Golden Triangle" of Northern Thailand (a region where the opium poppy grows indigenously and where rates of opioid dependence are high) in order to study the genetics of OD in one of several ethnic (i.e., Hmong) hill tribes. We have identified what appears to be an ideal geographically and culturally isolated village of approximately 2,500 inhabitants (1750 Hmong descended from 4 primary families/clans) of whom roughly 200 villagers are reported to have a lifetime history of OD (i.e., estimated lifetime prevalence rates 2.10%). The presence of apparent historical bottlenecks, cultural prohibitions against marrying outside the tribe, large and intact pedigrees, and relative absence of other drugs of abuse are likely to contribute to greater genetic and/or environmental homogeneity. In the current revised application, we propose to establish the feasibility of conducting a comprehensive, community-wide collection of all eligible subjects from extended Hmong pedigrees extensively characterized for opioid (and other substance) dependence using the SSADDA (Semi-Structured Assessment of Drug Dependence and Alcoholism) Specifically, a total of 200 Hmong villagers will be studied over a 2-vear period. Pedigree relationships will be established by interview and confirmed by genetic methods. Such studies, we believe, afford significant, perhaps uniquely powerful, advantages for identifying susceptibility loci for OD. [unreadable] [unreadable] [unreadable] [unreadable]